(157) Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden – a real-world study using registry data linked to the French national claims database

Publication Number: 1152

Background: CCALD is a rare X-linked genetic neurologic disease. It is diagnosed at around 7 years of age and leads to a dramatic neurologic regression within months and premature death that may be prevented with allogenic stem cell transplantation (HSCT). To the best of our knowledge, no comprehensive study on real-world data is available on CCALD.

Objectives: To describe the epidemiology, characteristics, management, and burden of patients with CCALD in France.

Methods: This was a real-life retrospective study using data from the French national ALD registry (LeukoFrance Database – DB), linked to the French national health data system (SNDS). LeukoFrance DB gathers most of the clinical, molecular, and biologic data from more than 2,000 families with leukodystrophy. SNDS is an exhaustive claims DB including diagnoses and healthcare consumptions from 99% of French population. Patients with CCALD identified in SNDS between 2009 and 2018 and successfully linked with LeukoFrance DB were included. Among them, those with ≥6 months of data post-inclusion were followed until the end of study or death. Main outcomes were the number and characteristics of patients with CCALD, history of HSCT, economic burden of CCALD, patients’ overall survival (OS) and major functional disability (MFD)-free survival (MFS). MFD included communication loss, movement loss, blindness, incontinence, wheelchair use and enteral feeding. OS and MFS were assessed using Kaplan-Meier method [CI95%].

Results: Among the 83 patients from LeukoFrance DB, 77 (92.7%) were successfully linked, 52 fulfilled CCALD selection criteria, and 47 had a sufficient follow-up. The median annual incidence rate was 4 cases, diagnosed at a median (Q1–Q3) age of 7.0 (6.0–9.0) years. One third (n=18, 38.3%) underwent a HSCT, done 4.9 (1.4–19.9) months after diagnosis in median. Five-year OS and MFS were 94.4% [66.6% ; 99.2%] and 72.2% [45.6% ; 87.4%] among patients with HSCT. These rates were 66.6% [41.0% ; 83.2%] and 31.9% [14.6% ; 50.6%] without HSCT. Patients without HSCT were hospitalized longer with 21.1 (2.8–89.6) days versus 6.2 (1.0–13.6) days in median by year. Median annualized costs were higher among patients without HSCT, with €35,602.8 (7,772.3–74,663.5) versus €6,833.1 (1,515.5–47,837.1) despite the high cost of HSCT itself.

Conclusions: This is the first national, multi-database, real-world study on CCALD, combining both clinical and biologic data from a national registry, and the exhaustiveness of a national claims database. Early HSCT is currently the only treatment available in France. When undergone, HSCT drastically increases patients’ survival and decreases CCALD burden. However, due to the lack of donors and a diagnosis errancy during childhood, it is done in a small proportion of patients.